870487-04-0Relevant articles and documents
A Wireframe DNA Cube: Antibody Conjugate for Targeted Delivery of Multiple Copies of Monomethyl Auristatin E
Gothelf, Kurt V.,M?rcher, Anders,Nijenhuis, Minke A. D.
supporting information, p. 21691 - 21696 (2021/09/02)
In recent years, several antibody drug conjugates (ADC) have been accepted by the FDA as therapeutics against cancer. It is well-known that control of drug-to-antibody ratio (DAR) is vital for the success of an ADC, which inspires the advancement of bette
BIOACTIVE CONJUGATE, PREPARATION METHOD THEREFOR AND USE THEREOF
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Paragraph 0321-0322, (2020/11/13)
The disclosure relates to a bioactive molecule conjugate, preparation methods and use thereof, particularly relates to a novel bioactive molecule conjugate obtained by improving coupling of the drug and the targeting moiety in an ADC or SMDC, as well as its preparation method and use in the manufacture of a medicament for the treatment of a disease associated with an abnormal cell activity.
NEW TARGETED CYTOTOXIC RATJADONE DERIVATIVES AND CONJUGATES THEREOF
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Paragraph 00171; 00172, (2019/02/25)
The present invention is directed to novel natural product-derived ratjadone-based compounds useful as payloads (or toxins) in drug-conjugates constructs with cell target binding moieties (CTBM) and payload-linker compounds useful in connection with drug conjugates. The present invention further relates to new ratjadone compositions including the aforementioned payloads, payload-linkers and drug conjugates, and methods for using these payloads, payload-linkers and drug conjugates, to treat pathological conditions including cancer, inflammatory and infectious diseases.
ANTI-EGFR ANTIBODY DRUG CONJUGATES
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Paragraph 0928, (2019/06/07)
The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.
BIOCOMPATIBLE AND HYDROPHILIC POLYMER CONJUGATE FOR TARGETED DELIVERY OF AN AGENT
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Paragraph 0487, (2019/11/04)
The present invention provides a biocompatible and hydrophilic polymer conjugate comprising a linear, aliphatic copolymer backbone to which is conjugated a binding moiety and an agent. The binding moiety is conjugated to an end of the copolymer backbone a
Improved Methodology for the Synthesis of a Cathepsin B Cleavable Dipeptide Linker, Widely Used in Antibody-Drug Conjugate Research
Mondal, Deboprosad,Ford, Jacob,Pinney, Kevin G.
supporting information, p. 3594 - 3599 (2018/09/11)
Antibody-drug conjugates (ADCs) represent an emerging class of biopharmaceutical agents that deliver highly potent anticancer agents (payloads) selectively to tumors or components associated with the tumor microenvironment. The linker, responsible for the connection between the antibody and payload, is a crucial component of ADCs. In certain examples the linker is composed of a cleavable short peptide which imparts an additional aspect of selectivity. Especially prevalent is the cathepsin B cleavable Mc-Val-Cit-PABOH linker utilized in many pre-clinical ADC candidates, as well as the FDA approved ADC ADCETRIS (brentuximab vedotin). An alternative route for the synthesis of the cathepsin B cleavable Mc-Val-Cit-PABOH linker is reported herein that involved six steps from l-Citrulline and proceeded with a 50% overall yield. In this modified route, the spacer (a para-aminobenzyl alcohol moiety) was incorporated via HATU coupling followed by dipeptide formation. Importantly, this route avoided undesirable epimerization and proceeded with improved overall yield. Utilizing this methodology, a drug-linker construct incorporating a potent small-molecule inhibitor of tubulin polymerization (referred to as KGP05), was synthesized as a representative example.
Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity
Wei, Binqing,Gunzner-Toste, Janet,Yao, Hui,Wang, Tao,Wang, Jing,Xu, Zijin,Chen, Jinhua,Wai, John,Nonomiya, Jim,Tsai, Siao Ping,Chuh, Josefa,Kozak, Katherine R.,Liu, Yichin,Yu, Shang-Fan,Lau, Jeff,Li, Guangmin,Phillips, Gail D.,Leipold, Doug,Kamath, Amrita,Su, Dian,Xu, Keyang,Eigenbrot, Charles,Steinbacher, Stefan,Ohri, Rachana,Raab, Helga,Staben, Leanna R.,Zhao, Guiling,Flygare, John A.,Pillow, Thomas H.,Verma, Vishal,Masterson, Luke A.,Howard, Philip W.,Safina, Brian
supporting information, p. 989 - 1000 (2018/01/01)
Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.
SILVESTROL ANTIBODY-DRUG CONJUGATES AND METHODS OF USE
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Page/Page column 81; 82; 83, (2018/01/15)
The invention relates generally to a silvestrol molecule activated with a leaving group. The invention further relates generally to an antibody-drug conjugate comprising an antibody conjugated by a linker to one or more silvestrol drug moieties and methods of treatment.
DRUG-LINKER CONJUGATE PHARMACEUTICAL COMPOSITIONS
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Paragraph 000159, (2017/05/02)
Compositions are disclosed having a cytotoxic and/or vascular disrupting agent (VDA) payload attached to a linker. The linker can be a cathepsin B protease cleavable linker or a non-cleavable linker that may degrade intracellularly. Methods for making and using the compositions are also provided. The compositions can be provided to a patient in need thereof with the composition coming into contact with a cancer cell to activate or release the cytotoxic and/or vascular disrupting agent payload.
ANTI-CD98 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
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Page/Page column 595, (2018/01/17)
The invention relates to anti-CD98 antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.